Measles Eradication: Recommendations from a Meeting Cosponsored by the World Health Organization, the Pan American Health
Organization, and CDC

Summary

Recent successes in interrupting indigenous transmission of
measles virus in the Americas and in the United Kingdom prompted
the World Health Organization (WHO), Pan American Health
Organization (PAHO), and CDC to convene a meeting in July, 1996 to
consider the feasibility of global measles eradication.
Presentations at the meeting included an overview of global
measles control and elimination efforts; detailed reviews of
successful measles elimination efforts in Latin America, the
English-speaking Caribbean, Canada, and the United States;
surveillance for clinical disease; laboratory tools for antibody
detection and virus identification; and other factors that might
influence the feasibility of disease eradication. With this
background information, meeting organizers asked participants to
address five questions:

Is global measles eradication feasible?

Is measles eradication feasible with current vaccines?

What are the appropriate vaccination strategies for measles
eradication?

How should surveillance for measles be carried out?

What role should outbreak control play in the strategy to
eliminate measles?

Participants agreed that measles eradication is technically
feasible with available vaccines and recommended adoption of the
goal of global eradication with a target date during 2005-2010,
with the proviso that measles eradication efforts should not
interfere with poliomyelitis eradication but should build on the
successes of the global Poliomyelitis Eradication Initiative.
Although existing vaccines are adequate for eradication,
vaccination strategies that rely on administration of a single
dose of vaccine are not. In the Americas, sustained interruption
of indigenous measles virus transmission has been achieved through
a three-tiered vaccination strategy that includes a) "catch-up"
vaccination of all persons aged 1-14 years, regardless of disease
history or vaccination status; b) "keep-up" vaccination of greater
than or equal to 90% of children in each successive birth cohort
at age 12 months; and c) "follow-up" campaigns designed to
vaccinate all persons within a specific age range whenever the
number of susceptible persons in the preschool-aged population
approximates the size of a typical birth cohort (in practice,
every 3-5 years). In other regions, different strategies may be
optimal.

Surveillance, a critical component of any strategy to
eliminate or eradicate measles, has two functions: to assess the
effectiveness of the measles elimination strategy and to detect
circulation of measles virus in a population. Systematic
surveillance based on clinical diagnosis should be implemented
early in any measles elimination program. In countries attempting
to eliminate indigenous measles, all isolated cases of measles and
at least one case in each chain of transmission should be
confirmed by laboratory tests. Specimens for virus isolation
(e.g., urine, nasopharyngeal swabs, or blood) should be collected
in conjunction with field investigations. Vaccination campaigns
generally have not proved to be effective responses to measles
outbreaks. Outbreaks should be treated as opportunities to
reinforce surveillance and to identify measures to prevent future
outbreaks.

The major obstacles to measles eradication are not technical
but perceptual, political, and financial. Measles is often
mistakenly perceived as a mild illness. This misperception, which
is particularly prevalent in industrialized countries, can inhibit
the development of public and political support for the allocation
of resources required for an effective elimination effort. The
disease burden imposed by measles should be documented,
particularly in industrialized countries, so that this information
can be used to educate parents, medical prac-titioners, public
health workers, and political leaders about the benefits of
measles eradication.

INTRODUCTION

During the early 1980s, in the aftermath of smallpox
eradication, some scientists and public health officials urged
consideration of a global effort to eradicate measles (1). During
the mid-1980s, however, the high level of population immunity
required to interrupt measles virus transmission became clear, and
the prospect of measles eradication seemed to recede (2). As
recently as 1993, a task force on disease eradication declared
measles "not now eradicable"(3). The major obstacles to
eradication cited by the task force were the contagiousness of
measles, the lack of a vaccine that is effective among children
aged less than 9 months (most of whom have maternal antibody to
measles that protects them from disease but which also inhibits
the immune response to the vaccine virus), and the incorrect
perception that measles is a mild illness.

Recent successes in implementing new approaches to control
and eliminate measles virus transmission prompted the World Health
Organization (WHO), the Pan American Health Organization (PAHO),
and CDC to convene a meeting July 9-10, 1996, in Atlanta to
reconsider the feasibility of global measles eradication. Among
the participants were representatives of the sponsoring
organizations, representatives of regions and countries that have
implemented measles elimination activities, and persons affiliated
with WHO Regional Offices, local and state health departments in
the United States, and universities. During the meeting,
presenters reviewed vaccination strategies and achievements in
measles control in the Caribbean and Latin America, Canada, and
the United States.

In addition, representatives of Denmark, Kuwait, Mexico,
South Africa, and the United Kingdom described their recent
efforts to control or eliminate measles transmission. In each of
these countries, intensification of efforts to control measles has
been followed by sustained declines in the number of reported
cases.

Other presentations addressed surveillance for clinical
disease and laboratory tools for virus identification and antibody
detection. Information was presented concerning other factors that
could potentially affect the feasibility of measles eradication
(i.e., the possible existence of nonhuman reservoirs for the
virus, the possibility of transmission of measles from persons
with asymptomatic measles infection, and the possibility that
vaccination-induced immunity to measles might wane with the
passage of time).

Based on this information and on subsequent discussion,
meeting participants were asked to address five questions:

Is global measles eradication feasible?

Is measles eradication feasible with current vaccines?

What are the appropriate vaccination strategies for measles
eradication?

How should surveillance for measles be carried out?

What role should outbreak control play in the strategy to
eliminate measles?

Discussion of these questions formed the basis for the
conclusions and recommendations of the meeting. The rapporteur
prepared a draft of the conclusions and recommendations that was
distributed and discussed in the final session of the 2-day
meeting. The discussion and subsequent modification of the draft
ensured that the report would reflect both points of consensus and
the sense of discussions among participants.

Definitions of Measles Elimination and Eradication

To facilitate communication among participants, working
definitions of two important terms were developed during the
meeting. Measles elimination refers to interruption of
transmission in a sizable geographic area in which vaccination
would nevertheless need to continue because of the continued
threat of reintroduction of the virus. Eradication, defined as the
global interruption of measles transmission, represents the sum of
successful elimination efforts in all countries. Once eradication
is achieved, vaccination could be stopped without risk for measles
outbreaks.

BACKGROUND

This section a) describes the status of global measles
control; b) summarizes efforts to eliminate measles in Latin
America, the English-speaking Caribbean, and Canada; and c)
describes progress toward measles elimination in the United
States. The summaries are based upon material presented at the
meeting and have been updated by the presenters.

Status of Global Measles Control

Since the inception of the World Health Organization's
Expanded Programme on Immunization (EPI) in 1974, the numbers of
cases and deaths attributed worldwide to measles have declined
substantially, from an estimated 100 million cases and 5.8 million
deaths in 1980 to an estimated 44 million cases and 1.1 million
deaths in 1995. In 1974, only 5% of the world's children aged 12-23
months had been vaccinated against measles. By the mid-1980s,
measles vaccination coverage among children aged 12-23 months in
developing countries had reached only 42%, largely because of the
lack of infrastructure for delivering vaccines and the perception
that measles was not a serious public health problem (4). From
1985 through 1990, however, the number of measles cases reported
worldwide declined by 56% as governments, international agencies
and other organizations provided the human and financial resources
needed to reach the global goal of 80% infant immunization
coverage by the year 1990 (WHO, unpublished data).

Despite these achievements, measles remains one of the
leading causes of child mortality in developing countries,
responsible for approximately 10% of all deaths among children
aged less than 5 years (5). These deaths typically occur among
young children in countries with low vaccination coverage levels.
Even countries that have achieved high levels of measles
vaccination coverage and have recorded several years of low
incidence frequently have experienced large measles outbreaks
(6-9).

On the basis of vaccination coverage, case fatality rates,
and vaccine effectiveness, WHO estimates that by 1995
measles-associated morbidity and mortality had decreased by 78%
and 88%, respectively, in comparison with the pre-vaccine era
(WHO, unpublished data).

Although these estimates demonstrate a marked reduction in
the health burden of measles, they also indicate that the
mid-decade goals of reducing measles morbidity by 90% and measles
mortality by 95% have not been met. Measles outbreaks have
continued to occur because, even in countries with high
vaccination coverage, the proportion of children susceptible to
the disease increases over time and eventually reaches a level
that sustains measles transmission. Ongoing measles outbreaks have
been particularly problematic in developing countries. Low
vaccination coverage has been primarily responsible for these
outbreaks. However, the practice of vaccinating children aged less
than 12 months has also contributed because the vaccine is less
effective among children of this age. (Vaccinating of children
aged less than 12 months has also substantially reduced measles
incidence in this age group, in which mortality from the disease
is highest.) Compared with vaccinating children aged greater than
or equal to 12 months, vaccinating those younger than 12 months
hastens the accumulation of susceptible persons in the
preschool-aged population.

In some developing countries, two-dose measles vaccination
schedules were introduced to slow the increase of susceptible
children by vaccinating those who had missed the first dose and
providing protection to those who did not develop an immune
response after a single dose of measles vaccine. This strategy has
interrupted measles transmission in some industrialized countries
that have achieved vaccination coverage levels exceeding 95% for
both doses of vaccine. Attainment of such high coverage levels
required active follow-up of children who missed a scheduled dose
(10). In developing countries, outbreaks have continued to occur
after two-dose schedules were implemented, because the second dose
(scheduled at ages ranging from 18 months to primary- or secondary
school entry) seldom reached previously unvaccinated children, and
coverage attained with the second dose is always lower than with
the first dose (11).

Since 1994, a strategy of limited vaccination campaigns
targeting all children aged 9 months to 5 years has been advocated
to reduce measles morbidity and mortality by reaching unvaccinated
children in areas in which risk for measles is high (e.g., large,
densely populated urban and peri-urban centers)(12). This strategy
is intended to improve vaccination coverage and not necessarily to
interrupt measles virus transmission. Several countries in WHO's
Southeast Asian Region (i.e., Bangladesh, India, Myanmar, and
Nepal), and its Western Pacific Region (i.e., the Philippines)
have used the strategy with only modest success. Many children who
were unvaccinated before the campaigns remained unvaccinated
afterward. In addition, poor case surveillance hindered efforts to
evaluate the impact of the campaigns in reducing the disease
burden.

The experience in the Philippines provides an example of
these difficulties. Immediately after a measles vaccination
campaign that targeted urban areas in that country, a measles
epidemic occurred. The epidemic prompted a vaccination coverage
survey, which indicated that the campaign had succeeded in
vaccinating only 44% of previously unvaccinated children
(Philippine Ministry of Health, unpublished data). Although
vaccination campaigns limited to high-risk areas can help reduce
morbidity and mortality caused by measles, they do not result in
the sustained interruption of measles virus transmission. Such
campaigns must include provisions for vaccinating previously
unvaccinated children and improving surveillance so that the
impact of the campaign can be measured.

The impact of measles vaccination has varied substantially
among the six WHO Regions (Figure_1). These interregional
differences reflect disparities in routine immunization coverage
levels and, more importantly, in the effectiveness of different
measles control strategies. Of the six WHO Regions, the most
substantial progress in measles control has been achieved in the
Americas, where most countries have implemented a strategy based
on a one-time-only mass vaccination campaign across a wide age
group. The goals of this strategy are to achieve a rapid reduction
in the number of susceptible children in the population and to
interrupt the transmission of measles virus. To keep the
susceptible population from exceeding the epidemic threshold
requires high routine coverage and periodic "follow-up" campaigns
to vaccinate children born after the previous campaigns. A
strategy similar to that used in the Americas has been implemented
or is being considered in at least one country in each of the
other WHO regions. For example, mass campaigns that included
children aged less than or equal to 16 years have been conducted
in the United Kingdom in the European Region, Bhutan and Mongolia
in the Western Pacific Region, Kuwait and Oman in the Eastern
Mediterranean Region, and South Africa in the African Region.

Measles Elimination in Latin America, the English-Speaking
Caribbean, and Canada

After the eradication of wild poliovirus from the Americas
was certified in 1994, the ministers of health of the countries of
the region established the goal of eliminating measles virus
circulation in the Western Hemisphere by the year 2000 (13). To
achieve this goal, PAHO has developed a measles elimination
strategy (14) that shares certain features with the successful
poliomyelitis eradication strategy being implemented throughout
the world (15). In addition to careful measles surveillance, the
PAHO measles elimination strategy has three main components.
First, a one-time-only "catch-up" measles vaccination campaign is
conducted, targeting all children aged 9 months through 14 years
without regard to previous history of measles disease or
vaccination. The goal is to interrupt measles virus circulation
rapidly by achieving high levels of measles immunity across a wide
age cohort. Early in the implementation of the PAHO measles
eradication strategy, some "catch-up" vaccination campaigns
targeted only children who lacked documentation of measles
vaccination. For several reasons, these campaigns were less
successful than later "nonselective" campaigns that targeted all
children without regard to disease history or vaccination status.
Problems identified in the early "selective" campaigns included
difficulties in determining the vaccination status of children and
failure to vaccinate the small proportion of children who remained
susceptible to the disease after receiving a previous dose of
measles vaccine.

After a "catch-up" campaign, efforts are directed at
strengthening routine vaccination services for infants to slow the
accumulation of susceptible preschool-aged children and to
maintain the interruption of measles virus circulation. This
component of the strategy is referred to as "keep-up" vaccination.
Because interruption of measles virus transmission reduces an
infant's risk for exposure to measles, the recommended age of
routine measles vaccination can be safely increased from 9 months
to 12 months. The concomitant increase in measles vaccine efficacy
reduces the percentage of vaccinated children who remain
susceptible to the disease (16). Efforts are made to achieve at
least 90% coverage in each successive birth cohort in every
district of every country.

Because measles vaccine is less than 100% effective and
universal vaccination coverage is rarely achieved, the number of
susceptible infants and children inevitably increases over time,
thus increasing the risk for a measles outbreak if the virus is
reintroduced. To reduce the number of susceptible preschool-aged
children, periodic "follow-up" vaccination campaigns are conducted
that target all children aged 1-4 years, regardless of vaccination
status or disease history. These campaigns are designed to protect
susceptible children from measles, whether they are susceptible
because they were not vaccinated or because they did not develop
a protective immune response to previous vaccination. The
vaccination coverage obtained through routine vaccination services
dictates the interval between "follow-up" campaigns, which are
conducted when the estimated number of susceptible preschool-aged
children approaches the number of infants in an average birth
cohort (in practice, every 3-5 years).

The first "catch-up" campaign in the Americas was conducted
during 1987 in Cuba; 98% coverage with measles-mumps-rubella (MMR)
vaccine was achieved in the population aged 9 months to 14 years.
In 1991, all countries of the English-speaking Caribbean conducted
a "catch-up" campaign with either single-antigen measles vaccine
or MMR vaccine. Vaccination coverage exceeded 90%. By the end of
1995, all countries of Latin America also had conducted "catch-up"
campaigns. The estimated measles vaccination coverage for children
aged 1-14 years in the countries of Latin America and the
English-speaking Caribbean exceeded 93%.

Since 1994, "follow-up" campaigns have been conducted in
Belize, Brazil, Chile, Colombia, Costa Rica, Cuba, El Salvador,
Guatemala, Jamaica, Nicaragua, Panama, and Peru (17). The
remaining countries in Latin America and the Caribbean are
planning to conduct similar campaigns by the end of 1998.

To monitor progress toward measles elimination in the
Americas, efforts have been made to strengthen measles
surveillance in every country. The goal of the PAHO measles
surveillance system is rapid detection of measles virus
circulation. In Latin America and the Caribbean, greater than
20,000 health units report weekly on the presence or absence of
suspected measles cases in their jurisdictions. At least one
reporting unit operates in every district or municipio
(municipality) in every country of Latin America and the
Caribbean.

For surveillance purposes, any patient in whom a clinician
suspects measles virus infection is considered to have a suspected
case of measles. Health-care workers are requested to report all
suspected cases immediately to local health authorities. To
determine whether suspected measles cases are actually caused by
measles infection, field epidemiologists attempt to investigate
every reported suspected case in a timely manner. Collecting a
serum sample for laboratory analysis is an essential part of such
investigations.

Because other pathogens and conditions can produce clinical
findings that resemble measles, only laboratory investigation can
provide the information needed to confirm or discard suspected
measles cases. Health-care workers are asked to collect a single
serum specimen from every patient suspected to have measles at the
time this presumptive diagnosis is made. In state or national
laboratories, serum specimens are tested with an enzyme
immunoassay (EIA) for the presence of measles IgM antibodies (14).
Specimens are screened initially with a commercial indirect IgM
measles assay that is sensitive but nonspecific. All specimens
that are positive or indeterminate by the indirect assay, as well
as a 10% random sample of negative sera, are sent to one of 11
regional reference laboratories in the PAHO measles laboratory
network for confirmatory testing with the more specific
IgM-capture EIA developed by CDC (18).

A suspected measles case is classified as
laboratory-confirmed if both the indirect and capture EIAs
indicate the presence of measles IgM antibodies in a properly
collected serum specimen or if there is an epidemiologic link to
another laboratory-confirmed measles case. An epidemiologic link
is defined as exposure to a person with a previous or subsequent
laboratory-confirmed case of measles. A suspected measles case can
be discarded only if a properly collected serum sample tests
negative for the presence of measles IgM antibodies. The case is
classified as clinically confirmed if a) no serum specimen is
collected from a patient who has a suspected case, and b) the case
investigation does not reveal an epidemiologic link to a
laboratory-confirmed measles case. Such clinically confirmed cases
are considered to represent failures of the measles surveillance
system, because the epidemiologic investigation was not properly
conducted.

In addition, PAHO has developed surveillance indicators to
measure the effectiveness and quality of national measles
surveillance systems. These indicators include the proportions of:

specimens for which laboratory results are available within 7
days of receipt in the laboratory.

As experience accumulates, these indicators may be modified
if the process of assessing surveillance can be simplified without
discarding information needed to improve national measles
surveillance systems.

After the 1977 initiation of the EPI in the Americas, measles
vaccination coverage increased steadily, measles incidence
declined, and the intervals between measles epidemics lengthened.
However, a regionwide measles epidemic occurred in 1990, when
218,000 measles cases were reported in Latin America and the
Caribbean. During this measles epidemic, the number of cases
reported approached the number reported in 1977. The "catch-up"
measles vaccination campaigns, conducted in Cuba in 1987 and in
other Caribbean and Latin American countries during 1991-1994,
immediately reduced the number of reported measles cases
(Figure_2).
During 1995, 13,340 suspected measles cases were reported from
Latin American and Caribbean countries (Table_1). Of these,
9,517
(71.3%) were discarded because IgM serology results were negative,
441 cases (3.3%) were confirmed by positive measles IgM laboratory
results, and 3,382 cases (25.3%) were classified as clinically
confirmed because of an incomplete epidemiologic investigation.

The total of 3,823 confirmed measles cases reported during
1995 from Latin America and Caribbean countries constitutes the
lowest annual total ever reported for the region and represents a
reduction of greater than 98% compared with the number reported in
1990. Measles is now rare in Latin America and the Caribbean.
Surveillance evaluations conducted during 1995 and 1996 in El
Salvador, Mexico, and Nicaragua found no evidence of measles virus
circulation. During 1996, a provisional total of 864 confirmed
measles cases was reported for Latin America and the Caribbean. Of
the total, 70 (8.1%) were confirmed by positive serologic tests
for measles IgM antibody. The remaining cases were classified as
clinically confirmed because laboratory investigations were not
conducted.

The last laboratory-confirmed case of measles detected in the
English-speaking Caribbean was reported in 1991, just before the
mass vaccination campaign was conducted. Similarly, the last
laboratory-confirmed cases of measles in Cuba and Chile were
detected in 1993. In other Latin American and Caribbean countries,
measles transmission is occurring at extremely low levels, if at
all. Most laboratory-confirmed cases have been sporadic and
isolated in time and place.

Importations of measles cases from Latin America detected by
the United States measles surveillance system provide an indirect
measure of the impact of the PAHO measles elimination strategy
(Figure_3). In 1990, greater than 200 cases, or greater than
80%
of all cases of measles imported to the United States, came from
Latin America (principally Mexico). Since then, the number and
proportion of measles cases imported from Latin America have
declined markedly. The last laboratory-confirmed case of measles
imported from Latin America or the Caribbean to the United States
was reported in 1994.

Canada accounts for only 4% of the population of the
Americas. In 1995, however, Canada reported 2,362 measles cases,
or nearly 40% of all measles cases reported in the Western
Hemisphere during that year. The routine measles vaccination
schedule introduced in the mid-1960s (i.e., a single dose of
measles-containing vaccine administered to children at age 12
months) had resulted in a 95% reduction in measles incidence, but
did not interrupt measles virus transmission. Although Canada
consistently reached coverage levels of greater than or equal to
97% with a single dose of measles-containing vaccine among
children aged 2 years, measles outbreaks continued to occur,
mostly among school-aged children. Outbreaks occurred even in
populations with documented vaccination rates approaching 100%.
Control measures such as exclusion from school and emergency mass
revaccination proved disruptive, costly, and of limited
effectiveness. Although in 1992 a National Conference on Measles
Control had endorsed the goal of eliminating indigenous measles
from Canada by 2005, little progress had been made by 1995.
Competing developments in childhood vaccination programs preempted
the formal introduction of a two-dose measles vaccination program
in Canada. The numbers of cases in Canada in 1995 contrasted with
numbers reported from other countries in the Americas and prompted
the adoption of a national goal of measles elimination -- with the
needed political support -- in late 1995.

Several analyses clarified the benefits of efforts to achieve
the elimination of measles in Canada. Mathematical modeling and a
Delphi survey predicted that there were enough susceptible persons
in the Canadian population to produce an annual average of 12,800
measles cases. An outbreak involving greater than or equal to
20,000 measles cases, 2,000 cases with complications, and several
measles-related deaths was predicted to occur as early as April
1996 unless additional strategies to eliminate measles were
implemented. Mathematical modeling also predicted that phasing in
a two-dose vaccination schedule by administering a second dose
only to young children would not eliminate measles for 10-15 years
and that a national "catch-up" campaign was the only way to avoid
the predicted epidemic and prevent an estimated 58,530 cases
during the next several years. A cost-benefit analysis indicated
that a measles vaccination campaign would save more than 2.5
dollars for every dollar expended (Laboratory Centre for Disease
Control, Ottawa, unpublished data).

In late 1995, the National Advisory Committee on Immunization
recommended a mass measles vaccination campaign. By July 1996, six
provinces (comprising 80% of Canada's population) had completed
"catch-up" vaccination campaigns for all school-aged children: in
some provinces this included children aged greater than or equal
to 18 months, as well. Two additional provinces began
implementation of a "catch-up" program in the fall of 1996. More
than 4 million children received supplementary vaccinations and
provincial coverage for the target populations averaged
approximately 90%. Furthermore, all of Canada's provinces or
territories have introduced a second MMR vaccination for children
aged 18 months or 4-6 years, depending on the province.

These successful vaccination campaigns produced immediate
results: three measles outbreaks that had begun in early 1996 were
quickly terminated as the campaigns began. Only 324 cases of
measles were reported in Canada for 1996; most of these cases
occurred before May, usually the month when incidence is highest.
Transmission of measles virus appears to have been interrupted
during fall, 1996. The same strategies should be implemented in
the remaining provinces to ensure the sustained interruption of
measles virus transmission because of the continuing problem of
measles importations from countries where measles transmission
continues.

Measles Elimination in the United States

The United States is in the midst of a third attempt to
eliminate indigenous transmission of measles. Earlier efforts,
initiated in 1966 and 1978, suppressed measles incidence to levels
below any previously recorded; 1,497 cases were reported in 1983,
the fewest in any year before the 1990s. Implementation of state
requirements for vaccination with measles-containing vaccine as a
condition for school entry was one of the major factors in
increasing vaccination coverage and reducing the incidence of
measles (19). Low levels of measles transmission persisted through
the mid-1980s. An average of 2,900 cases was reported each year
during 1983-1988. However, during 1989-1991, the United States
experienced a resurgence of measles, during which 55,622 cases
were reported. The largest increase in incidence occurred among
preschool-aged children. Most cases occurred among children who
had not been vaccinated. This increase in measles cases prompted
a major effort to ensure vaccination against measles at the
recommended age. In 1994, the Childhood Immunization Initiative
established specific goals for vaccination coverage and disease
reduction (20). For measles, the goal for first-dose coverage was
90% by 1996 and the elimination of indigenous measles by 1996.
These goals have largely been achieved.

Before the measles resurgence during 1989-1991, measles
vaccination coverage levels among children aged 2 years had never
reached 70% (21). Since 1991, coverage levels with
measles-containing vaccine have increased to 91% (22). These
improvements in coverage have been achieved through locally
initiated efforts (e.g., linking immunization services with the
Special Supplemental Nutrition Program for Woman, Infants, and
Children (WIC) and a program that coupled assessment of coverage
levels among providers with feedback) (23-24).

In 1989, the Advisory Committee on Immunization Practices and
the American Academy of Pediatrics recommended that children in
the United States receive two doses of measles-containing vaccine.
This recommendation was made to prevent outbreaks in schools;
several well-documented outbreaks demonstrated that measles
transmission could occur even with coverage levels greater than
95% for a single dose of measles vaccine (25-27). States have
gradually implemented requirements that mandate a second dose of
measles-containing vaccine as a condition for entering school. For
the 1996-97 school year, 35% of school-age children in the United
States were covered by such requirements (CDC, unpublished data).
Records of doses of MMR vaccine purchased and administered suggest
that as many as 65% of school-age children have received a second
dose of measles-containing vaccine (CDC, unpublished data).

As a result of these efforts, a sustained decline in measles
incidence occurred in the United States beginning in 1993, when
312 confirmed measles cases were reported. The reported number of
cases increased to 963 in 1994; outbreaks among members of groups
that oppose vaccination were largely responsible for the increase.
In 1995, a total of 309 cases was reported, the fewest since
national surveillance began.

In addition to the decline in reported cases, epidemiologic
evidence suggests that indigenous measles transmission has been
interrupted. From September 12 through December 31, 1993, 25
confirmed cases of measles were reported. Of these, seven cases
were classified as imported and 14 as importation-associated cases
(i.e., cases linked to a chain of transmission originating with an
imported case). The four cases classified as indigenous were not
clustered geographically or temporally. They occurred in widely
separated geographic locations -- California, Florida, upstate New
York, and Rhode Island. These cases were also widely separated in
time -- periods of 4 weeks and 6 weeks occurred during which no
indigenous cases were identified. These data suggest that the four
indigenous cases (if they were, in fact, measles and not some
other illness misclassified because of false-positive laboratory
test results) more likely resulted from exposure to undetected
imported cases than from ongoing indigenous transmission of
measles virus.

Molecular epidemiologic studies of wild-type measles virus
also indicate that indigenous measles transmission was interrupted
during 1993. Measles viruses isolated from throughout the United
States during 1988-1993 were similar, suggesting a single
predominant lineage (28). Since 1993, that lineage has not been
detected in the United States, except in one case imported from
the Philippines. Numerous wild-type measles viruses isolated since
1993 have been similar to strains circulating outside the United
States. Strains similar to those found in Western Europe and East
Asia were particularly common in 1996 (Figure_4).

During October and November 1995, a 6-week period occurred
during which all cases of measles reported in the United States
were either imported or linked to an imported case. A similar
4-week period was observed during February 1996. During late 1996
and early 1997, a 16-week period occurred when a single indigenous
case was identified. These data suggest that indigenous measles
transmission in the United States has been interrupted numerous
times and that, in each instance, transmission of the disease has
been re-established by an importation of measles virus.

Since 1992, imported cases have made up an increasing
proportion of all measles cases reported in the United States. The
number of imported cases detected has declined from an average of
120 per year during 1985-1992 to 53 per year since 1993. This
reduction is almost entirely the result of decreases in imported
cases from Latin America (Figure_3). Since 1994, only one case
that could possibly have been imported from a Latin American
country has been reported, and subsequent investigation revealed
no evidence of measles transmission in that country. Since 1992,
most measles cases imported to the United States have originated
in Western Europe and East Asia, reflecting relatively poor
control of measles in these regions and frequent travel to the
United States.

CONCLUSIONS AND RECOMMENDATIONS

The five questions posed to meeting participants (see
Introduction) were designed to structure discussion of the
feasiblity of and strategies for measles eradication. The
conclusions and recommendations developed by participants in
response to these questions follow.
Feasibility of Measles Eradication
Conclusions:

Based on the success of efforts to control measles in the
Western Hemisphere and the United Kingdom, global measles
eradication is technically feasible with available vaccines.
National, subregional, and regional elimination of measles can and
should be accomplished. Although nonhuman primates can be infected
with measles virus, such nonhuman reservoirs are unlikely to
sustain measles transmission. Although asymptomatic and
nonclassical cases of measles can occur among vaccinated persons,
these atypical cases would not impede elimination or eradication
of the virus. Waning immunity does not appear to play a major role
in vaccine failure.
Recommendations:

A goal of global measles eradication should be established,
with a target date during 2005-2010. Factors that favor a global
initiative to eradicate measles within this time frame include:

the expected success of poliomyelitis eradication by 2000,

the success of measles elimination campaigns in the Americas
and the United Kingdom,

the urgency of measles eradication because of expected
epidemiologic changes resulting from routine measles vaccination
programs (i.e., the accumulation of a growing population of
susceptible adults),

the predicted favorable benefit-cost ratio, and

the recognition of measles as a major public health problem in
many developing countries.

Although measles eradication is a logical addition to and
extension of the poliomyelitis eradication initiative, the effort
should build on the success of poliomyelitis eradication.
Consequently, measles eradication should not be undertaken
immediately and simultaneously in all parts of the world. Rather,
measles eradication efforts should await maturation of the
poliomyelitis eradication program in each region of the globe, and
should be implemented as countries and regions become free of
poliomyelitis. Because of the rapid accumulation of persons
susceptible to measles, the implementation phase of an eradication
effort should be compressed into as brief a time as possible.
Research into the molecular pathogenesis of measles and the immune
response to measles virus infection should continue.

Vaccination Strategies
Conclusions:

Existing vaccines are sufficient to eradicate measles, but
eradication requires more than a routine one-dose vaccination
strategy. However, no single two-dose approach is optimal for all
countries. Success has been attained in many countries,
particularly in the Americas, with a strategy comprising a)
"catch-up" mass campaigns during which all persons aged 1-14 years
are vaccinated, regardless of prior vaccination status; b) high
routine ("keep up") vaccination coverage following the "catch-up"
campaign; and c) periodic "follow-up" campaigns during which all
children aged 1-4 years are vaccinated. In some countries with
highly developed vaccination programs capable of reaching greater
than 95% coverage, an ongoing two-dose "plus" strategy appears
capable of eventually eliminating measles. (The "plus" refers to
special supplementary efforts to reach populations at high risk.)
Regardless of the strategy selected, monitoring the accumulation
of susceptible persons within the population is essential.
Accumulation of susceptible persons occurs because a single dose
of vaccine does not elicit a protective immune response in some
children and because some children are not vaccinated. Such
monitoring permits appropriate action, in the form of "follow-up"
campaigns or special vaccination activities in areas at highest
risk.

Recommendations:

Countries that adopt a strategy of measles elimination should
implement some form of "catch-up" vaccination rather than simply
adding a second dose to the routine vaccination schedule. All
children must receive measles vaccine, and the "second dose"
should also reach those who missed the first dose; such children
should be vaccinated and should subsequently receive another dose.
Exploration of alternative methods of vaccine delivery,
particularly jet injectors, and of alternative preparations of the
vaccine should continue.

Surveillance Strategies
Conclusions:

Measles case surveillance is a critical component of any
strategy to control measles, including strategies to eliminate or
eradicate measles. The most important functions of surveillance
are to assess the effectiveness of the strategy and to detect
circulation of measles virus in a population, rather than to
identify every case of measles infection (except during the final
stages of eradication). Although a passive system of surveillance
for measles may be adequate in countries or regions where
health-care providers detect and report measles cases, active
surveillance is required in many circumstances (e.g., areas where
notification of suspected cases is low, where a confirmed case has
been identified, where clusters of suspected cases have been
reported, or where a dense population of unvaccinated children
exists). As more countries interrupt measles transmission,
importation of measles virus will become more prominent. Because
determining the source of an imported case can be difficult, the
following classification scheme for confirmed measles cases may be
useful: indigenous; source unknown; imported (source known); and
imported (source unknown). Surveillance indicators are a useful
means of evaluating the performance of surveillance systems but
must be limited in number to be optimally effective. No external
standard for determining the completeness of measles surveillance
exists that is equivalent to the rate of acute flaccid paralysis
for poliomyelitis.

Recommendations:

Surveillance for individual measles cases should be
implemented at an early stage of the elimination program. Measles
notification should be based on clinical suspicion rather than
rigid case definitions. Case definitions are important, however,
during investigation and classification of suspected cases. To
establish the source of imported measles cases, collaboration
among countries can be facilitated by WHO offices. Experience in
using measles surveillance indicators is limited, and proposed
indicators may be modified based on accumulating experience.

Laboratory Strategies
Conclusions:

Laboratory confirmation of suspected measles cases will
become increasingly important as measles incidence declines and
countries progress toward elimination. Establishment of a
functioning global network of reference diagnostic laboratories
will be a critical element in achieving global eradication.
Development of a rapid field diagnostic test would facilitate
surveillance and case investigations. In addition to confirmation
of cases, the laboratory has a vital role in characterizing
measles virus isolates to determine whether cases represent
sustained indigenous transmission or importations. The laboratory
can also serve an important function in surveillance for measles
immunity because serologic measures may be useful in confirming
the level of protection estimated by vaccination coverage of a
population.

Recommendations:

In countries attempting to eliminate measles, all isolated
cases of measles and at least one case from each chain of
transmission should be confirmed by laboratory tests. In addition
to serum or saliva specimens for laboratory confirmation,
specimens for virus isolation should be collected within 7 days of
rash onset in conjunction with case investigations. Specimens that
can be cultured for virus isolation include urine, nasopharyngeal
swabs, and blood. Reference laboratories with expertise in
culturing measles virus should perform virus isolation.
Development of a rapid field diagnostic test is the most urgent
research need.

Response to Measles Outbreaks
Conclusions:

Preventing measles outbreaks is more effective than trying to
contain them. Mass vaccination campaigns undertaken in response to
outbreaks are of limited usefulness in most countries because such
efforts are costly, disruptive, and often ineffective by the time
they are instituted. Careful investigation of all outbreaks,
however, can generate data needed to obtain the political support
required for an effective elimination effort. In addition,
outbreak investigations can help determine why transmission of
measles occurred; such investigations will be critical to refining
measles elimination strategies as they are implemented.
Recommendations:

Measles outbreaks should be treated as opportunities to
reinforce surveillance, assess the health burden of continuing
measles transmission, and identify appropriate measures to prevent
future outbreaks.

Obstacles to Eradication
Conclusions:

The major obstacles to measles eradication are perceptual,
political, and financial. The full health impact of measles is
often underestimated. Measles is frequently perceived as a minor
illness of little consequence, particularly in industrialized
countries. This perception may make it difficult to develop the
political support necessary to carry out a successful global
eradication effort. Strong support for measles eradication can be
expected in many developing countries, where measles is recognized
as a major killer. Measles eradication will quickly pay for itself
because of savings in vaccinations, hospitalizations, and deaths
prevented.

Recommendations:

Parents, medical practitioners, and public health
professionals -- particularly those in industrialized countries --
must be educated about the global disease burden imposed by
measles. The disease burden of measles should be better documented
in more countries, especially in the developed world, to gain
support for global eradication.

DISCUSSION

This 2-day consultative meeting represents a landmark in the
history of measles control. The data presented demonstrated the
feasibility of interrupting measles transmission for prolonged
periods over wide geographic areas. Recently developed molecular
tools allow researchers to distinguish indigenous from imported
virus strains. Data developed with these tools support the claim
that transmission of indigenous strains of measles virus has been
interrupted for substantial periods in the Americas and in the
United Kingdom. In addition, global experience has now
demonstrated that an important distinction must be made between
the limited measles vaccination campaigns that have targeted urban
or poorly served areas in many countries and the strategy that has
interrupted measles transmission in the Americas and the United
Kingdom. Limited campaigns targeted to underserved or high-risk
populations may improve vaccination coverage, but they are not
sufficient to interrupt transmission of the virus. Countries
should undertake such geographically limited campaigns only as
part of a larger measles control or elimination strategy.

Presentations from representatives of individual countries
and WHO regions documented the political and public interest in
the eradication of measles, particularly among developing
countries. However, global consensus and commitment are essential
because measles eradication will require supplementary vaccination
activities in industrialized countries as well as in developing
countries. In countries and regions where endemic poliovirus
transmission continues, poliomyelitis eradication efforts must be
further strengthened to ensure that the introduction of measles
elimination activities builds on the successes of the global
poliomyelitis eradication initiative. A global plan of action for
the eradication of measles is needed to facilitate coordination
among countries, donors, technical agencies, and international
organizations and to ensure that eradication activities are
conducted efficiently.
References:

Birkhead GS, LeBaron CW, Parsons P, et al. The immunization of
children enrolled in the Special Supplemental Food Program for
Women, Infants, and Children (WIC): the impact of different
strategies. JAMA 1995;274:312-6.

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